BackgroundThe human breast comprise several ductal systems, or lobes, which contain a small amount of fluid containing cells, hormones, proteins and metabolites. The complex physiology of these ducts is likely a contributing factor to the development of breast cancer, especially given that the vast majority of breast cancers begin in a single lobular unit.MethodsWe examined the levels of total protein, progesterone, estradiol, estrone sulfate, dehydroepiandrosterone sulfate, and macrophages in ductal fluid samples obtained from 3 ducts each in 78 women, sampled twice over a 6 month period. Samples were processed for both cytological and molecular analysis. Intraclass correlation coefficients and mixed models were utilized to identify significant data.ResultsWe found that the levels of these ductal fluid components were generally uncorrelated among ducts within a single breast and over time, suggesting that each lobe within the breast has a distinct physiology. However, we also found that estradiol was more correlated in women who were nulliparous or produced nipple aspirate fluid.ConclusionsOur results provide evidence that the microenvironment of any given lobular unit is unique to that individual unit, findings that may provide clues about the initiation and development of ductal carcinomas.

Miniature solenoids routinely enhance small volume nuclear magnetic resonance imaging and spectroscopy; however, no such techniques exist for patients. We present an implantable microcoil for diverse clinical applications, with a microliter coil volume. The design is loosely based on implantable depth electrodes, in which a flexible tube serves as the substrate, and a metal stylet is inserted into the tube during implantation. The goal is to provide enhanced signal-to-noise ratio (SNR) of structures that are not easily accessed by surface coils. The first-generation prototype was designed for implantation up to 2 cm, and provided initial proof-of-concept for microscopy. Subsequently, we optimized the design to minimize the influence of lead inductances, and to thereby double the length of the implantable depth (4 cm). The second-generation design represents an estimated SNR improvement of over 30% as compared to the original design when extended to 4 cm. Impedance measurements indicate that the device is stable for up to 24 h in body temperature saline. We evaluated the SNR and MR-related heating of the device at 3T. The implantable microcoil can differentiate fat and water peaks, and resolve submillimeter features.

A magnetic resonance imaging device includes an elongate flexible member having a proximal end, a distal end, and a lumen extending between the proximal end and the distal end and a solenoid coil affixed to the distal end of the elongate flexible member, the solenoid coil having a plurality of wire turns, the solenoid coil connected to a twisted-pair of leads extending proximally along the length of the flexible member. A connector is disposed at the proximal end of the elongate flexible member, the connector operatively coupled to the twisted-pair of leads. In an alternative embodiment, a coaxial cable substitutes for the lumen-containing elongate flexible member.

The physiology of the nonlactating human breast likely plays a key role in factors that contribute to the etiology of breast cancer and other breast conditions. Although there has been extensive research into the physiology of lactation, few reports explore the physiology of the resting mammary gland, including mechanisms by which compounds such as hormones, drugs, and potential carcinogens enter the breast ducts. The purpose of this study was to explore transport of exogenous drugs into ductal fluid in nonlactating women and determine if their concentrations in the fluid are similar to those observed in the breast milk of lactating women. We selected two compounds that have been well characterized during lactation, caffeine and cimetidine. Caffeine passively diffuses into breast milk, but cimetidine is actively transported and concentrated in breast milk. After ingestion of caffeine and cimetidine, 14 nonlactating subjects had blood drawn and underwent ductal lavage at five time points over 12 h to measure drug levels in the fluid and blood. The concentrations of both caffeine and cimetidine in lavage fluid were substantially less than those observed in breast milk. Our results support recent evidence that the cimetidine transporter is not expressed in the nonlactating mammary gland, and highlight intriguing differences in the physiology and molecular transport of the lactating and nonlactating breast. The findings of this exploratory study warrant further exploration into the physiology of the nonlactating mammary gland to elucidate factors involved in disease initiation and progression.

Nearly one hundred years ago, the English surgeon and author, Sir Geoffrey Keynes, wrote “the breast is a gland which throughout life is exhibiting some secretory activity, the difference between a lactating and a non-lactating breast being one partly of degree and partly of the chemical constitution of the secretion” (Keynes 1923). While knowledge about the histopathology of breast cancer has progressed significantly in the subsequent years, the intraluminal cells and secretions of the ductal system in the non-lactating or resting breast have received little attention. Most pathologists have considered these cells and secretions to be sloughed off degenerating epithelium and proteinaceous material and of little biological interest (Petrakis 1986). However, there has been isolated interest in looking more carefully at this fluid and determining its physiology and its clinical significance.

Abstract The majority of breast cancers are thought to initiate in the lining of the 6 to 8 ducts that exit the nipple. Evidence suggests that the presence of nipple aspirate fluid (NAF), and in particular NAF containing atypical epithelial cells, in the ducts is predictive of future breast cancer risk. Although NAF fluid and cells may be representative of a preneoplastic state, use of NAF has not proven to represent a robust indicator for future malignancy. Chronic infiltration of tissues by immune cells predisposes them to future malignancy. Since macrophages can represent up to half of the total cells recovered from NAF, and their presence within malignant breast tumors has predictive value in terms of survival, we hypothesized that changes in the inflammatory microenvironment of breast ducts may foster future malignancy and/or provide an early indicator of future neoplasia. To test this hypothesis, we conducted an exploratory study to investigate gene expression in NAF and ductal lavage fluid. We first used real-time PCR to quantitatively measure mRNA expression of select genes within the cellular milieu of NAF to determine if that microenvironment correlated with a tumor-promoting state. Expression of multiple genes was observed in 15 samples collected from healthy volunteers, with robust expression of myeloid-associated genes including CD14, CD68, CCL3, CSF1 and IL1B observed in the majority of samples. To determine whether similar inflammatory microenvironments were found within each duct, and whether they were comparable to those in NAF-containing ducts, ductal lavage (DL) samples were obtained from 4 different ducts at the same time as NAF collection. Out of 7 volunteers, 4 provided samples allowing comparison between NAF and DL, and between multiple ducts. Analysis of gene expression from these healthy volunteers indicated that gene expression differed between NAF samples and each DL sample. More importantly, unique gene expression was found for each duct sampled, indicating that the immune microenvironment within each duct is distinct from other ducts within the same breast. In order to identify a potential inflammatory gene signature, we then obtained NAF samples from patients with breast cancer that had not received neoadjuvant chemotherapy prior to surgery, from both the cancerous and contralateral breasts. With 4 patients analyzed, no consistent expression difference has thus far been observed, indicating either that the relevant genes have not been identified, or that analysis of inflammatory genes within NAF may not be a predictive method with which to evaluate risk of future malignancy in women that produce NAF. A larger study is warranted to further investigate the significance of inflammatory gene expression in breast ductal fluid. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-01-14.

Abstract Introduction: The incidence of breast cancer, the most common cancer in women, is very high in Western Countries and is increasing rapidly in the Third World. Yet, despite better screening, earlier diagnosis, and the development of new therapies, a cure for metastatic breast cancers remains an elusive goal. Since it is difficult to defeat breast cancer after it has occurred, finding new strategies to delay or prevent the development of breast cancer has been an important area for clinical and experimental investigations. Multinational studies have suggested that women who undergo a full-term pregnancy before the age of 20, with or without lactation, have about one half the risk of developing breast cancer compared to women who undergo their first pregnancy after the age of 35 or women who have never undergone a full term pregnancy. Thus, pregnancy at an early age protects against breast cancer development. This universal protective effect of pregnancy serves as a major clue and starting point in the search for new experimental strategies and novel biomarkers related to the prevention of breast cancer. Methods: Women were recruited who had never been diagnosed with breast cancer and fit in one of the following categories; 1) had their first child ≥25 years of age, 2) had their first child ≥35 years of age, and 3) a control group of women the same age as those in groups 1 and 2 but who have never given birth were recruited and provided a sample of breast tissue and blood simultaneously. These groups were categorized as early parous, late parous, or nulliparous and their RNA was isolated from tissue and whole blood. Human whole genome microarray analysis (Agilent) was performed to identify the genes that were persistently altered in expression due to early pregnancy. Results: The study of molecular alterations in breast cancer genes has succeeded in identifying some genetic mechanism of breast cancer development. We attempted to elucidate early pregnancy-related changes in genes in breast tissue and blood associated with resistance to breast cancer. Over 2200 genes were up-regulated 2 folds or more in the blood and breast of early parous women than late parous and nulliparous women. Approximately 5000 genes were down-regulated 2 folds or more in the blood and breast of early parous women compared to late parous and nulliparous women. Conclusion: These studies focused on the analysis of human breast tissue and blood to gain a deeper understanding of changes in parity associated with the protective effect of early pregnancy in women. From these altered gene expressions we have identified a gene signature for early parity. The persistently altered genes will be used as novel biomarkers to predict breast cancer risk and develop strategies to protect the breast from cancer development. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-14.

Background: There is a need to facilitate research aimed at finding the cause and prevention of breast cancer. A deterrent has been the difficulty basic scientists have in involving normal women in clinical research. However, the Dr Susan Love Research Foundation has had success in recruiting healthy community women for studies. In 2006 we partnered with a Texas Tech University scientist who had planned to do his research in an animal model because he felt it would be impossible to obtain blood and core needle biopsies from the women fitting his strict criteria. However by accessing our registry of potential volunteers we were able to collect all the specimens. A grant from the Avon Foundation for Women allowed us expand and to develop the Love/Avon Army of Women (AOW). Methods: The AOW was launched in October 2008 by Dr. Love on national media- to recruit one million women who are willing to participate in clinical research into the cause and prevention of breast cancer. Researchers contact the AOW and apply for access to the AOW. Projects are reviewed by the AOW Scientific Advisory Committee which includes members nominated by the AACR and the NBCC. If a researcher cannot obtain his or her own specimens, there are regional AOW Centers where the appropriate data and samples can be collected according to the specifications of the scientist. The criteria and procedures of approved AOW studies are e-mailed to the entire AOW database allowing viral distribution beyond the registry. Women self-select and sign up for studies on-line after a secondary screen. Researchers are responsible for explaining the study and will report back to the participating women the overall findings of the study via webcast once completed ensuring a partnership between the women and the researchers while educating women in the way research is conducted. Results: As of June 2009, over 286,000 women have become Army of Women members by signing up at www.armyofwomen.org. Members of all races/ethnicities ranging in ages from 18 to 100 are represented. There are members in all 50 states as well as many countries throughout the world. Twenty per cent of members are breast cancer survivors while the rest are unaffected. Since October 2008, the AOW has recruited for ten studies. All have had a rapid and substantial response, continually far exceeding the researcher9s expectations. Five were closed within a week. Over 11,000 women have participated in AOW supported clinical research studies. Efforts are underway to launch a large online cohort study enabling collection of cross-sectional and longitudinal data that can be accessed to address specific questions in survivors and unaffected women. Conclusions: The Love/Avon Army of Women is an available resource for epidemiologists and basic scientists who have projects that need human breast tissue, ductal fluid, urine, saliva or blood as well as data. This novel resource allows breast cancer scientists to obtain exactly the type of specimens and information they need when they need it and promises to revolutionize research and accelerate efforts to eradicate breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3075.

Researchers are using the intraductal approach to advance breast cancer risk assessment, prevention, diagnosis, and treatment. Procedures and technologies that can access and interrogate the ductal-alveolar systems include nipple aspiration, ductal lavage and ductoscopy. Ductoscopic papillectomy, ductoscopic margin evaluation, and intraductal therapy are considered promising investigational and innovative treatments. These techniques are used to explore the biology of the normal breast; collect and analyze breast fluid and cells to identify biomarkers that can be used in breast cancer detection and risk assessment; and to identify new ways to find and administer therapeutic and/ or preventive agents to the breast tissue. This report summarizes the latest research findings in these areas, presented at The 6 International Symposium on the Intraductal Approach to Breast Cancer in 2009. Introduction: The human breast is composed of multiple ductal lobular systems that each open onto the surface of the nipple. These ductal systems arborize into ductal trees with associated lobules and are lined with epithelial cells, where most breast cancers are thought to originate. The application of suction to the nipple openings (nipple aspiration) and ductal lavage are used to collect fluid and exfoliated cells from the breast ducts. Many substances associated with the growth, development, and tumorigeneses of the breast have been detected in breast fluids. Cytological techniques have shown that breast cancer-associated abnormalities can be found in these cells [1–6]. In addition, the production and cytological properties of nipple aspirate fluid are associated with breast cancer risk, with long-term follow-up of women undergoing nipple aspiration having shown that breast cancer risk is two to five times greater in women diagnosed with cytologic atypia than it is for women who do not yield fluid [7]. The first International Intraductal Symposium was held in 1999. A biennial event, the Symposium includes discussions and presentations on the anatomy and physiology of the normal and diseased breast, advances in intraductal technologies, findings from genetic, epigenetic, and proteomic analyses of intraductal fluid, and the latest translational research on intraductal approaches to breast cancer risk assessment, diagnoses, and treatment. The 6 International Symposium on the Intraductal Approach to Breast Cancer, sponsored by the Dr. Susan Love Research Foundation and held in Santa Monica, California, on 19–21 February 2009, was attended by more than 100 delegates from 14 countries, including clinicians, epidemiologists, pathologists, basic scientists, translational investigators, and breast cancer advocates. The program included talks by 34 invited speakers and 16 pilot grant applicants in sessions that addressed the etiology of breast cancer; biomarkers of risk in nipple aspirate fluid and ductal lavage; anatomy, ductoscopy, and breast imaging; and intraductal therapy. Delegates also had the opportunity to attend demonstrations of ductoscopy, sonoductography, and nipple aspirate fluid collection on live volunteers. Minisymposium on a Novel Etiology for Breast Cancer: Inflammation: The first session’s speakers discussed the role that inflammation, nipple aspirate fluid and macrophages may play in breast cancer development. Lisa Coussens (University of California, San Francisco, USA) discussed her research with an MMTV-PyMT mouse model of mammary carcinogenesis that revealed a tumor-promoting role for TH2-CD4 T effector cells. These novel findings suggest the immune system modulates the early onset of cancer development in specific organs, and confirmed epidemiological studies showing that increased macrophage presence correlates with higher tumor grade and decreased survival. Eliminating the T effector cells did not regulate primary disease, and also made it more likely that the cancer would metastasize to the lung, behavior that appeared to be regulated by macrophages. These findings could one day translate into an immune signature that is an independent predictor of recurrence risk, while identifying the pro-tumor mechanisms could lead to new cancer treatments. Premalignant cell damage in the breast duct lining signals a biochemical cascade that delivers inflammatory proteins to the cell site. Chandice Covington (Texas Tech University Health Services Center, Lubbock, TX, USA) discussed one of these proteins, C-Reactive. CRP is associated with cancer risk, and has BioMed Central

1535 Background: One of the barriers to finding the cause of breast cancer is the difficulty basic scientists have in involving healthy women and obtaining human tissues, fluids, and information processed according to their needs. The Dr. Susan Love Research Foundation has collaborated with basic scientists successfully recruiting community women for studies. These efforts led to the Love/Avon Army of Women (AOW), a new "just in time" resource seeking to partner women with scientists to find the cause and prevention of breast cancer.METHODSThe AOW is a pool of volunteers who have registered online ( www.armyofwomen.org ) that they are willing to participate in research. Peer-reviewed, funded projects submitted by researchers are reviewed by the AOW Scientific Advisory Committee for eligibility. An eBlast is sent to all AOW volunteers describing the study, and eligible women RSVP to the AOW for a secondary screen. The list is then sent to the researcher. If needed, referrals are made to a regional AOW Center for specimen collection, processing, and shipment. All scientists participate in a webcast with the eligible volunteers to explain the research before the study and describe the overall results at the end, ensuring a partnership between the women and the investigators.RESULTSAOW recruitment was initiated October 1, 2008, by Dr. Love on national media with the goal of creating a resource of 1,000,000 women available for researchers. To date over 260,000 women have joined. All ethnicities, ages (18-89), and states are represented. The first eBlast was sent out in mid-October for the Sister Study to accrue the last 5,000 women needed from diverse backgrounds. In 48 hours, 1,600 women had responded and qualified, and in 2 months, 2,500 had signed up with a 90% enrollment rate. The second study required women who were breastfeeding and scheduled for a breast biopsy. In one week, 30 eligible women were identified.CONCLUSIONSThe Love/Avon Army of Women is a just in time resource for breast cancer scientists to obtain exactly the specimens: breast or adipose tissue, ductal fluid, urine, saliva, blood, or information processed exactly as needed. This new partnership between women and scientists promises to revolutionize research and accelerate efforts to find the cause and prevention of breast cancer. No significant financial relationships to disclose.

The majority of breast cancers originate in the mammary ducts. As such many diagnostic techniques introduce mm-diameter devices into the ducts through the nipple. Established intraductal techniques include ductal lavage, and white-light or fluorescence endoscopy. While reported values vary, these techniques typically suffer from low sensitivity and specificity. Similarly, Magnetic Resonance Imaging (MRI) for breast oncology suffers a high rate of false positives. Magnetic resonance (MR) spectroscopy is highly effective in distinguishing between benign and malignant tissue. However, clinical relevance is limited to late-stage of disease due to a required cubic-centimeter volume for diagnosis. Small-volume sensitivity for spectroscopy and imaging is possible through use of a miniature radio-frequency (RF) coil. An intraductal RF microcoil reduces the required volume of diseased tissue to a cubic-millimeter, bringing spectroscopy to early stages of early diagnosis. Micro-scale images from an intraductal microcoil may enable high-precision localization of tumors and tumor margins. The microcoil catheter was designed with an approximate diameter of 1 mm for intraductal use and for possible integration with ductoscopes. Experimental verification of the first-generation coil-design was achieved through ex vivo MR imaging of tissue. As expected, the microcoil provided microscale images. While 3-T (128 MHz) MRI typically provides 1 to 30 voxels per-cubic-mm the MRI microcoil can provide hundreds, and even thousands of voxels in the same volume. The first generation microcoil consisted of a 1-mm-diameter solenoid with 4.5 turns, spaced 0.05 mm apart, leading to 25-mm long parallel leads, with one of the leads passing through the center of the solenoid. A crucial requirement for optimal MR coil design is a homogenous magnetic field generated in the coil. Unfortunately, the central conductor inside the solenoid of the original microcoil greatly disturbed the homogeneity of the magnetic-field. The parallel-leads of the first generation device correspond to a popular catheter-coil geometry, a single-loop coil. The parallel leads therefore collect unwanted signal, in other words noise. The new design overcomes both of these flaws. Turn-spacing of the first microcoil design was intended for optimizing the signal collected from the center of the solenoid. However, since the target tissue is at the tip of the solenoid, the new design is optimized for our target tissue with ten turns separated by the thin insulation of the wire. The turn-spacing of the first generation microcoil was controlled by a thick layer of insulation that also provided a good barrier from the body. Due to the lack of a thick insulator, the second generation-design required a new configuration for isolating the coil from the body to prevent degradation of the performance over time. We analyzed the stability of the new microcoils by soaking 5 microcoils in body temperature saline and measuring the impedance at 128 MHz over time. The impedance of the microcoils remained constant for nearly 2 hours, and increased only slightly after 4 hours. Preliminary heating experiments indicate that little to no heating occurs during use of the microcoil as an MR transceiver. Initial imaging results confirm that the second generation microcoil improves greatly on the first generation coils, with significantly less imaging artifacts despite having twice the lead length. Recent success by Dr. Love with intraductal chemotherapy application intensifies the need for early diagnosis. A microcoil may provide spectroscopic evidence of cancer. Microcoil images may show if the malignancy has breached the ductal lining. The open lumen of the intraductal microcoil enables clinicians to target sub-branches of ducts with chemotherapy.

Abstract B23 Introduction Ten years ago the NCI published an Executive Summary stating that it is “clear that a more complete understanding of the normal mammary gland...will be a critical underpinning of continued advances in detecting, preventing and treating breast cancer.” A deterrent to obtaining this understanding has been the difficulty basic scientists have in involving normal women in their research. The Love/Avon Army of Women, is a “just in time” tissue and data resource launched to give researchers access to the samples/data they need in an attempt to accelerate research into the cause and prevention of breast cancer. Background The Dr Susan Love Research Foundation piloted the concept of a “just in time” database in Southern California recruiting over 700 women who were willing to consider participating in clinical research. As new studies arise the women are informed and if appropriate decide whether to participate. In 2006, we expanded our pilot when we agreed to partner with Texas Tech University in a study titled “Analysis of Parity-Induced Protection in Human Breast and Serum.” Initially the PI planned to do research in an animal model because he felt it would be impossible to obtain blood and breast core needle biopsies from 44 women each year, 11 who had their first child before 25, 11 women who had their first child after 35 and 22 age-matched nulliparous controls. By accessing our registry of healthy women and reaching out to other less-traditional communities, such as nuns and lesbians, we have been able to collect all the specimens to date for the study. The Avon Foundation has also been able to recruit volunteers at their Walks for other Avon grants. These experiences led us to launch this joint venture, the Love/Avon Army of Women, to extend this experience to any scientist who needs it. Methods Starting Oct 1, 2008 one million women will be recruited from around the country who are willing to participate in clinical research. They will sign up on a website with minimal information. Scientists who need access to human breast tissue, ductal fluid, urine, saliva or blood as well as those collecting data for epidemiology studies will contact the AOW through the website. Once a grant has been awarded by an outside funder, the research will be reviewed for appropriateness for the AOW. Then an eblast will go out to all members of the AOW describing the study, the criteria for participation as well as what will be involved. Women will self select and RSVP to the AOW. After undergoing a secondary screen they will either be referred to the researcher directly or to an Army center where the appropriate data and specimens will be collected according to the specifications of the scientist. All scientists will be required to participate in a webcast with all the women who have responded to explain the research question and how this study will move us forward in finding the cause and prevention of breast cancer. Again, after the study has been completed the researcher will report back to the participating women the overall findings of the study via webcast. This will ensure a partnership between the women and the researchers in moving towards the goal of eradicating breast cancer. Conclusions The Love/Avon Army of Women is a novel resource for breast cancer scientists to obtain exactly the type of specimens they need when they need it. This new partnership between women and scientists can revolutionize research and accelerate efforts to eradicate breast cancer. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B23.

Abstract B65 Background The majority of breast cancers originate in the ductal epithelium of the breast. Ductal lavage provides a minimally invasive tool for assessing epithelial cells and their microenvironment. Previous studies of pathological atypical hyperplasia on biopsy, and cytological aypia in nipple aspirate fluid (NAF) and random fine needle aspiration (FNA) have suggested that these cells are precancerous because of the subsequent increased risk of cancer. It has therefore been hypothesized that serial ductal lavage could be used to identify atypia and monitor the effects of chemoprevention over time. This report is part of a larger study examining the differences in hormone levels and cytology between ducts and their reproducibility. This report presents a cohort of women unselected for risk who voluntarily underwent ductal lavage of the same ducts on two occasions six months apart. Samples were analyzed for epithelial cells and macrophages. Methods A total of 107 women were recruited in this IRB-approved prospective study to undergo ductal lavage of three fluid or non-fluid-yielding ducts within a breast. Women were unselected for risk: the average Gail score was 1.67 and ten women had a history of contralateral breast cancer. The average age was 51 years. Fifty-four women were premenopausal, 4 were perimenopausal and 49 were postmenopausal. Samples were submitted in a blinded fashion to a central laboratory and were analyzed by duct for both macrophage and epithelial cell number on Papanicolaou-stained slides. If adequate epithelial cells were present (>10), a diagnosis of each duct (benign, mild atypia, or marked aytpia) was made by an experienced cytopathologist. Results Of the 107 women, 317 (99%) ducts were successfully cannulated without regard to nipple aspirate fluid (NAF) production. Thirty ducts in 23 women were diagnosed with mild or marked atypia on either of the two visits. Of these ducts, 16 were diagnosed at the initial visit and 13 at the second visit. Only one duct was diagnosed with mild atypia on both visits, in a woman with a Gail score of 1.4. Cellular atypia in ductal lavage was not reproducible at a six month interval (p=0.45). This absence of reproducibility was seen in women at all risk levels. Macrophage and epithelial cell numbers also showed a lack of reproducibility at the six month interval (p=0.31 and p=0.22, respectively). Conclusion Atypia on cytology in ductal lavage in women unselected for risk was not reproducible at a six month interval, suggesting that a single diagnosis of atypia on lavage should not be used as a marker for the identification of women at risk. Further studies are necessary to indicate whether persistent atypia over an extended interval could represent an elevated risk for breast cancer. In addition, ongoing studies are being performed to identify better cellular markers of premalignancy and subsequent risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B65.

Implantable RF-coils have enabled sub-mm resolution magnetic resonance images (MRI) of deep structures. Scaling down the size of RF coils has similarly provided a gain in signal-to-noise ratio in nuclear-magnetic-resonance spectroscopy. By combining both approaches we designed, fabricated, and imaged with an implantable microcoil catheter. While typical implantable catheters use a transverse magneti-zation, the axial magnetization of the microcoil provides improved sensitivity and allows visualization of the tissue beyond the distal end of the catheter. The microcoil catheter was designed with a diameter of 1 mm for future integration with intracranial devices, and for intraductal use in breast oncology. We modified the NMR-microcoil design to allow implantation of the RF coil, by winding the microcoil on medical-grade silicone tubing and incorporating leads on the catheter to connect circuit components. In order to achieve proper turn spacing, we coated copper wire with 25 μm of biocompatible polymer (Parylene C). Tuning and matching circuitry insured that the impedance of the RF coil was approximately 50 Ω at the operating frequency for 3-T proton MR applications. A duplexer was used to enable use of the microcoil catheter as a transceiver. Experimental verification of the coil design was achieved through ex vivo imaging of neural tissue. As expected, the microcoil catheter provided microscale images with 20-μm in-plane-resolution and 170-μm-thick slices. While 3-T MRI typically provides 1 to 30 voxels per-cubic-millimeter, in this paper we report that the MRI microcoil can provide hundreds, and even thousands of voxels in the same volume.

BACKGROUND:Ductal lavage is a technique that samples the contents of breast ducts for research into the biology of breast cancer. Enthusiasm for this method has declined because of technical challenges associated with the procedure. These include: difficulty in duct cannulation, high levels of subject discomfort, and an inability to confirm perforation.METHODS:As part of a larger institutional review board (IRB)-approved study, consenting healthy women underwent ductal lavage of 3-4 ducts in one breast. Intranipple lidocaine was administered before duct cannulation. Ductoscopy was performed prior to catheterization and high-definition ultrasound was used for imaging during the lavage procedure. Pain scores were recorded at 24 hours and 2 weeks. Subjects were asked to return in 6 months for a repeat of the procedure.RESULTS:Ductoscopy was performed prior to lavage under real-time ultrasound 308 times in 107 subjects. There were 280 confirmed ducts (90.9%) and 21 perforations (6.8%), while seven (2.3%) were indeterminate. Subjects reported minimal discomfort, and 91% reported a 0 (0-10 range) pain score 2 weeks after the procedure. The retention rate was 90% at 6 months.CONCLUSION:The injection of lidocaine directly into the nipple greatly increases the feasibility of duct cannulation and improves subject comfort. Confirmation of duct cannulation and lavage can be documented with ductoscopy and ultrasound imaging. These procedures can be added to ductal lavage to facilitate its use as a research tool.